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Those who follow life sciences won’t have failed to pick up on the impact and controversy of two particular papers appearing in Nature at the end of January. The STAP (stimulus-triggered acquisition of pluripotency) studies by Obokata et al. at the Japanese RIKEN Center for Developmental Biology suggested that a lowering of environmental pH, from around 7 to 5.7, was enough to reprogram differentiated adult cells (‘somatic cells’) into pluripotent, or stem-cell-like, cells. Reprogramming somatic cells is currently performed by nuclear transfer or expression of the genes responsible for pluripotency, so evidence, however preliminary, that it could be done by environmental stimuli was naturally going to be big news.

Within 24 hours of appearing in Nature, the paper ‘Stimulus-triggered fate conversion of somatic cells into pluripotency‘ had already received a three-star ‘Exceptional’ rating on F1000Prime from Sharad Kumar. Prof. Kumar’s description of the article’s “profound ramifications for stem cell research” was soon followed by many more Recommendations from Faculty Members in different fields ranging from Developmental Biology to Nephrology, and the article quickly became one of the highest rated papers on F1000Prime.

However, question marks were beginning to appear over the paper, as the initial excitement turned to skeptical inquiry. The lack of any reproduction of the authors’ results by teams around the world made some question the whole concept. In his Recommendation of the paper at the beginning of March, Faculty Member D John Doyle provided a note of caution, pointing our readers in the direction of the bloggers whose concerns were raising alarm bells with regard to the paper’s results.

[pullquote]If this research pans out, I envision the authors being offered a trip to Stockholm. — D John Doyle[/pullquote]

Since then, Neuroscience Faculty Member Thierri Galli and his Associate Guan Wang have withdrawn their positive recommendation with a corrigendum stating, “If the method was to be proven irreproducible, our comments would not be valid anymore”. Rheumatology & Clinical Immunology Faculty Member Darwin Prockop‘s user comments directed the reader to the increasingly skeptical response to this paper in the media, fanned by the flames of one of the original authors calling for a retraction. At the time of writing, the most recent review on F1000Prime was a Dissenting opinion from cell biologist Brent Cochran. In his words “… the simplicity of the technique leads me to be skeptical. I hope I’m wrong”.

It must be remembered that the results of this impressive paper have not been disproved, but it does remind us, as Jalees Rehman points out in his excellent blog post for SciLogs, that “scientific peer review does not involve checking replicability of the results”. On F1000Prime, by way of example, the rise and fall of the infamous “arsenic paper” can be seen in the excitement that it initially garnered, followed by the critical counter-points made by many of our Faculty Members.

[pullquote] …the simplicity of the technique leads me to be skeptical. I hope I’m wrong. — Brent Cochran[/pullquote]

A paper, once published – much like science in general – does not remain static. It changes and is often confirmed, refuted, dis-refuted, and re-refuted until those precious few grains of truth remain. One of the beautiful things about post-publication peer-review is the fact that we can view this process in “real time” as experts from varying fields tell the story of a paper’s impact*.

Questions remain to be answered with these papers – and who knows? A replication of the results may be just around the corner – but we should look forward to following the often messy but nevertheless robust process of scientific debate.

*When editorial expressions of concern or full retractions occur for a recommended article, the F1000Prime editorial team will update the article on the F1000Prime site (as with this article by way of example). In addition, Faculty Members may follow up their Recommendations with addenda or corrigenda, including the option to withdraw their endorsement.